IE921463A1 - Fibrinogen receptor antagonists - Google Patents
Fibrinogen receptor antagonistsInfo
- Publication number
- IE921463A1 IE921463A1 IE146392A IE921463A IE921463A1 IE 921463 A1 IE921463 A1 IE 921463A1 IE 146392 A IE146392 A IE 146392A IE 921463 A IE921463 A IE 921463A IE 921463 A1 IE921463 A1 IE 921463A1
- Authority
- IE
- Ireland
- Prior art keywords
- mammal
- composition
- alkyl
- mmol
- rsp59
- Prior art date
Links
- 239000002319 fibrinogen receptor antagonist Substances 0.000 title claims abstract description 19
- 210000001772 blood platelet Anatomy 0.000 claims abstract description 47
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 29
- 108010049003 Fibrinogen Proteins 0.000 claims abstract description 18
- 102000008946 Fibrinogen Human genes 0.000 claims abstract description 18
- 230000002776 aggregation Effects 0.000 claims abstract description 18
- 238000004220 aggregation Methods 0.000 claims abstract description 18
- 229940012952 fibrinogen Drugs 0.000 claims abstract description 18
- 238000000034 method Methods 0.000 claims description 70
- 150000001875 compounds Chemical class 0.000 claims description 57
- 239000000203 mixture Substances 0.000 claims description 50
- 241000124008 Mammalia Species 0.000 claims description 41
- 230000015572 biosynthetic process Effects 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 34
- 208000007536 Thrombosis Diseases 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 26
- 239000001257 hydrogen Substances 0.000 claims description 25
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 208000005189 Embolism Diseases 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 23
- -1 chloro, bromo, iodo Chemical group 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 18
- 239000003937 drug carrier Substances 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 10
- 125000004104 aryloxy group Chemical group 0.000 claims description 10
- 239000003146 anticoagulant agent Substances 0.000 claims description 9
- 239000003527 fibrinolytic agent Substances 0.000 claims description 9
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 8
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 8
- 229940127219 anticoagulant drug Drugs 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 229960000103 thrombolytic agent Drugs 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 108010023197 Streptokinase Proteins 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 230000003287 optical effect Effects 0.000 claims description 6
- 125000004043 oxo group Chemical group O=* 0.000 claims description 6
- 229960005202 streptokinase Drugs 0.000 claims description 6
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims description 5
- 108010001014 Plasminogen Activators Proteins 0.000 claims description 5
- 102000001938 Plasminogen Activators Human genes 0.000 claims description 5
- 229960002897 heparin Drugs 0.000 claims description 5
- 229920000669 heparin Polymers 0.000 claims description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- 229940127126 plasminogen activator Drugs 0.000 claims description 5
- 229960005080 warfarin Drugs 0.000 claims description 5
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 claims description 5
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 4
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 4
- 229940127218 antiplatelet drug Drugs 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 4
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 229930192474 thiophene Natural products 0.000 claims description 4
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical group CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 3
- 240000005265 Lupinus mutabilis Species 0.000 claims description 3
- 235000008755 Lupinus mutabilis Nutrition 0.000 claims description 3
- 235000019095 Sechium edule Nutrition 0.000 claims description 3
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 3
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 239000001301 oxygen Chemical group 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 229910052717 sulfur Chemical group 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- 125000004471 alkyl aminosulfonyl group Chemical group 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 181
- 235000019439 ethyl acetate Nutrition 0.000 description 157
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 132
- 238000002360 preparation method Methods 0.000 description 113
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 104
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 104
- 239000000243 solution Substances 0.000 description 86
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 84
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 77
- 229910001868 water Inorganic materials 0.000 description 74
- 238000003818 flash chromatography Methods 0.000 description 69
- 239000011541 reaction mixture Substances 0.000 description 68
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 57
- 238000005481 NMR spectroscopy Methods 0.000 description 57
- 239000012267 brine Substances 0.000 description 53
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 53
- 239000000377 silicon dioxide Substances 0.000 description 46
- 239000003921 oil Substances 0.000 description 41
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- 239000007787 solid Substances 0.000 description 32
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- 239000000741 silica gel Substances 0.000 description 31
- 229910002027 silica gel Inorganic materials 0.000 description 31
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
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- 238000006243 chemical reaction Methods 0.000 description 26
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- UCMIRNVEIXFBKS-UHFFFAOYSA-N beta-alanine Chemical compound NCCC(O)=O UCMIRNVEIXFBKS-UHFFFAOYSA-N 0.000 description 24
- 239000012230 colorless oil Substances 0.000 description 24
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 24
- 101150041968 CDC13 gene Proteins 0.000 description 23
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- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 23
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 21
- 238000003756 stirring Methods 0.000 description 18
- 229910004373 HOAc Inorganic materials 0.000 description 16
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 16
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 16
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 16
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 15
- 150000001412 amines Chemical class 0.000 description 15
- 210000004369 blood Anatomy 0.000 description 13
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- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 229910017974 NH40H Inorganic materials 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 11
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 11
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 11
- GSQBIOQCECCMOQ-UHFFFAOYSA-N β-alanine ethyl ester Chemical compound CCOC(=O)CCN GSQBIOQCECCMOQ-UHFFFAOYSA-N 0.000 description 11
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- 239000002904 solvent Substances 0.000 description 10
- YEDUAINPPJYDJZ-UHFFFAOYSA-N 2-hydroxybenzothiazole Chemical compound C1=CC=C2SC(O)=NC2=C1 YEDUAINPPJYDJZ-UHFFFAOYSA-N 0.000 description 9
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
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- FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 7
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- 150000002148 esters Chemical class 0.000 description 7
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- 230000005764 inhibitory process Effects 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
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- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 5
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
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- 229910052906 cristobalite Inorganic materials 0.000 description 1
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 description 1
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- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- UCSVJZQSZZAKLD-UHFFFAOYSA-N ethyl azide Chemical compound CCN=[N+]=[N-] UCSVJZQSZZAKLD-UHFFFAOYSA-N 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 230000003480 fibrinolytic effect Effects 0.000 description 1
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- 235000013355 food flavoring agent Nutrition 0.000 description 1
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- SAVROPQJUYSBDD-UHFFFAOYSA-N formyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)=CO SAVROPQJUYSBDD-UHFFFAOYSA-N 0.000 description 1
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- 230000004927 fusion Effects 0.000 description 1
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- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N hydroxymaleic acid group Chemical group O/C(/C(=O)O)=C/C(=O)O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000008611 intercellular interaction Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- JXDYKVIHCLTXOP-UHFFFAOYSA-N isatin Chemical compound C1=CC=C2C(=O)C(=O)NC2=C1 JXDYKVIHCLTXOP-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
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- 239000012071 phase Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- OGHBATFHNDZKSO-UHFFFAOYSA-N propan-2-olate Chemical compound CC(C)[O-] OGHBATFHNDZKSO-UHFFFAOYSA-N 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 1
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- 238000010791 quenching Methods 0.000 description 1
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- 230000004044 response Effects 0.000 description 1
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- 235000012239 silicon dioxide Nutrition 0.000 description 1
- CLDWGXZGFUNWKB-UHFFFAOYSA-M silver;benzoate Chemical compound [Ag+].[O-]C(=O)C1=CC=CC=C1 CLDWGXZGFUNWKB-UHFFFAOYSA-M 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
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- 239000000758 substrate Substances 0.000 description 1
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- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- IONMNRHLZXJDJX-UHFFFAOYSA-N tert-butyl 4-(2-iodoethyl)piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(CCI)CC1 IONMNRHLZXJDJX-UHFFFAOYSA-N 0.000 description 1
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 239000010936 titanium Substances 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 229910052905 tridymite Inorganic materials 0.000 description 1
- JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/68—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
- C07D211/72—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D211/74—Oxygen atoms
- C07D211/76—Oxygen atoms attached in position 2 or 6
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/06—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing isoquinuclidine ring systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Hydrogenated Pyridines (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US69689391A | 1991-05-07 | 1991-05-07 | |
| US72035791A | 1991-06-25 | 1991-06-25 | |
| US87126292A | 1992-04-23 | 1992-04-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IE921463A1 true IE921463A1 (en) | 1992-11-18 |
Family
ID=27418643
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE146392A IE921463A1 (en) | 1991-05-07 | 1992-07-01 | Fibrinogen receptor antagonists |
Country Status (20)
| Country | Link |
|---|---|
| US (2) | US5281585A (fr) |
| EP (1) | EP0512831B1 (fr) |
| JP (1) | JP2531562B2 (fr) |
| KR (1) | KR920021531A (fr) |
| CN (1) | CN1067883A (fr) |
| AT (1) | ATE184874T1 (fr) |
| AU (1) | AU647618B2 (fr) |
| BG (1) | BG98194A (fr) |
| CA (1) | CA2068064C (fr) |
| DE (1) | DE69230013T2 (fr) |
| ES (1) | ES2137175T3 (fr) |
| FI (1) | FI934894A0 (fr) |
| HU (1) | HUT68769A (fr) |
| IE (1) | IE921463A1 (fr) |
| IL (1) | IL101779A0 (fr) |
| MX (1) | MXPA92002103A (fr) |
| NO (1) | NO933999D0 (fr) |
| NZ (1) | NZ242609A (fr) |
| WO (1) | WO1992019595A1 (fr) |
| YU (1) | YU47992A (fr) |
Families Citing this family (112)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5780303A (en) * | 1990-04-06 | 1998-07-14 | La Jolla Cancer Research Foundation | Method and composition for treating thrombosis |
| US6521594B1 (en) | 1990-04-06 | 2003-02-18 | La Jolla Cancer Research Foundation | Method and composition for treating thrombosis |
| US6017877A (en) * | 1990-04-06 | 2000-01-25 | La Jolla Cancer Research Foundation | Method and composition for treating thrombosis |
| US5672585A (en) * | 1990-04-06 | 1997-09-30 | La Jolla Cancer Research Foundation | Method and composition for treating thrombosis |
| WO1993018058A1 (fr) * | 1992-03-06 | 1993-09-16 | G.D. Searle & Co. | Imitateurs peptidiques utiles comme inhibiteurs de l'agregation plaquettaire |
| CA2150550A1 (fr) * | 1992-12-01 | 1994-06-09 | Melissa S. Egbertson | Antagonistes du recepteur du fibrinogene |
| DE4308034A1 (de) * | 1993-03-13 | 1994-09-15 | Cassella Ag | Neue Heterocyclen, ihre Herstellung und ihre Verwendung |
| US5563141A (en) * | 1993-03-29 | 1996-10-08 | Zeneca Limited | Heterocyclic compounds |
| US5750754A (en) * | 1993-03-29 | 1998-05-12 | Zeneca Limited | Heterocyclic compounds |
| US5652242A (en) * | 1993-03-29 | 1997-07-29 | Zeneca Limited | Heterocyclic derivatives |
| US5753659A (en) * | 1993-03-29 | 1998-05-19 | Zeneca Limited | Heterocyclic compouds |
| CZ250995A3 (en) * | 1993-03-29 | 1996-01-17 | Zeneca Ltd | Pyridine derivatives, process of their preparation and intermediates employed in this process as well as pharmaceutical compositions containing thereof |
| GB9313285D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Acid derivatives |
| US5463011A (en) * | 1993-06-28 | 1995-10-31 | Zeneca Limited | Acid derivatives |
| GB9313268D0 (en) * | 1993-06-28 | 1993-08-11 | Zeneca Ltd | Chemical compounds |
| WO1995008536A1 (fr) * | 1993-09-22 | 1995-03-30 | Fujisawa Pharmaceutical Co., Ltd. | Derives de n-(3-piperidinylcarbonyl)-beta-alanine utilises comme antagonistes du facteur d'agregation plaquettaire |
| AU7862794A (en) * | 1993-10-19 | 1995-05-08 | Sumitomo Pharmaceuticals Company, Limited | 2,3-diaminopropionic acid derivative |
| DE4427979A1 (de) * | 1993-11-15 | 1996-02-15 | Cassella Ag | Substituierte 5-Ring-Heterocyclen, ihre Herstellung und ihre Verwendung |
| US5446056A (en) * | 1993-11-24 | 1995-08-29 | The Du Pont Merck Pharmaceutical Company | Isoxazoline compounds useful as fibrinogen receptor antagonists |
| US5849736A (en) * | 1993-11-24 | 1998-12-15 | The Dupont Merck Pharmaceutical Company | Isoxazoline and isoxazole fibrinogen receptor antagonists |
| ATE198748T1 (de) * | 1993-11-24 | 2001-02-15 | Du Pont Pharm Co | Isoxazoline und isoxazole derivate als fibrinogen rezeptor antagonisten |
| US5523302A (en) * | 1993-11-24 | 1996-06-04 | The Du Pont Merck Pharmaceutical Company | Aromatic compounds containing basic and acidic termini useful as fibrinogen receptor antagonists |
| US5563158A (en) * | 1993-12-28 | 1996-10-08 | The Dupont Merck Pharmaceutical Company | Aromatic compounds containing basic and acidic termini useful as fibrinogen receptor antagonists |
| DE4405378A1 (de) * | 1994-02-19 | 1995-08-24 | Merck Patent Gmbh | Adhäsionsrezeptor-Antagonisten |
| US5821241A (en) * | 1994-02-22 | 1998-10-13 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| JPH09510442A (ja) * | 1994-03-11 | 1997-10-21 | ファーマコペイア，インコーポレイテッド | スルホンアミド誘導体及びそれらの使用 |
| WO1995025088A1 (fr) * | 1994-03-14 | 1995-09-21 | Merck & Co., Inc. | Ethylation pyridylique de derives de lactames |
| US5665882A (en) * | 1994-03-14 | 1997-09-09 | Merck & Co., Inc. | Pyridyl ethylation of lactams |
| US5451578A (en) * | 1994-08-12 | 1995-09-19 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| US5525617A (en) * | 1994-08-24 | 1996-06-11 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| US5686607A (en) * | 1994-09-16 | 1997-11-11 | Merck & Co., Inc. | Pyridyl ethylation of lactam derivatives |
| US5494921A (en) * | 1994-09-16 | 1996-02-27 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| AU691677B2 (en) * | 1994-11-01 | 1998-05-21 | Terumo Kabushiki Kaisha | Tetrahydroisoquinoline derivative and medicinal preparation containing the same |
| US5719144A (en) * | 1995-02-22 | 1998-02-17 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| US5674894A (en) * | 1995-05-15 | 1997-10-07 | G.D. Searle & Co. | Amidine derivatives useful as platelet aggregation inhibitors and vasodilators |
| ZA963391B (en) * | 1995-05-24 | 1997-10-29 | Du Pont Merck Pharma | Isoxazoline fibrinogen receptor antagonists. |
| US6187757B1 (en) | 1995-06-07 | 2001-02-13 | Ariad Pharmaceuticals, Inc. | Regulation of biological events using novel compounds |
| CA2234967A1 (fr) * | 1995-10-19 | 1997-04-24 | Merck & Co., Inc. | Antagonistes du recepteur de fibrinogene |
| US5852045A (en) * | 1995-10-19 | 1998-12-22 | Merck & Co., Inc. | Fibrinogen receptor antagonists |
| CA2242877A1 (fr) * | 1996-01-16 | 1997-07-24 | Merck & Co., Inc. | Antagonistes du recepteur integrine |
| US5952306A (en) * | 1996-01-16 | 1999-09-14 | Merck & Co., Inc. | Integrin receptor antagonists |
| KR19990087694A (ko) * | 1996-03-13 | 1999-12-27 | 후지야마 아키라 | 피브리노겐 수용체 길항제로서의 N-[(R)-１-{３-(４-피페리딜)프로피오닐-３-피페리딜카보닐]-２(S)-아세틸아미노-β-알라닌 |
| US5889023A (en) * | 1996-05-10 | 1999-03-30 | Merck & Co., Inc. | Fibrinogen receptor antagonist |
| GB2312895A (en) * | 1996-05-10 | 1997-11-12 | Merck & Co Inc | Fibrinogen receptor antagonists |
| US5935598A (en) * | 1996-06-19 | 1999-08-10 | Becton Dickinson Research Center | Iontophoretic delivery of cell adhesion inhibitors |
| US6004955A (en) * | 1996-08-15 | 1999-12-21 | Dupont Pharmaceuticals Company | Cyclic carbamates and isoxazolidines as IIb/IIIa antagonists |
| US5900414A (en) * | 1996-08-29 | 1999-05-04 | Merck & Co., Inc. | Methods for administering integrin receptor antagonists |
| US6211184B1 (en) * | 1996-08-29 | 2001-04-03 | Merck & Co., Inc. | Integrin antagonists |
| US5981546A (en) * | 1996-08-29 | 1999-11-09 | Merck & Co., Inc. | Integrin antagonists |
| JP2001500875A (ja) * | 1996-09-18 | 2001-01-23 | メルク エンド カンパニー インコーポレーテッド | 心臓血管系疾患関連の危険性を減らす併用治療法 |
| US5978698A (en) * | 1996-10-08 | 1999-11-02 | Merck & Co., Inc. | Angioplasty procedure using nonionic contrast media |
| US6063794A (en) * | 1996-10-11 | 2000-05-16 | Cor Therapeutics Inc. | Selective factor Xa inhibitors |
| US6194435B1 (en) | 1996-10-11 | 2001-02-27 | Cor Therapeutics, Inc. | Lactams as selective factor Xa inhibitors |
| US6369080B2 (en) | 1996-10-11 | 2002-04-09 | Cor Therapeutics, Inc. | Selective factor Xa inhibitors |
| US6262047B1 (en) | 1996-10-11 | 2001-07-17 | Cor Therapeutics, Inc. | Selective factor Xa inhibitors |
| US5919792A (en) * | 1996-10-30 | 1999-07-06 | Merck & Co., Inc. | Integrin antagonists |
| US5952341A (en) * | 1996-10-30 | 1999-09-14 | Merck & Co., Inc. | Integrin antagonists |
| US6017925A (en) * | 1997-01-17 | 2000-01-25 | Merck & Co., Inc. | Integrin antagonists |
| US5981584A (en) * | 1997-02-06 | 1999-11-09 | Merck & Co., Inc. | Fibrinogen receptor antagonist prodrugs |
| EP0977773A1 (fr) | 1997-04-14 | 2000-02-09 | Cor Therapeutics, Inc. | INHIBITEURS SELECTIFS DU FACTEUR Xa |
| AU6896298A (en) | 1997-04-14 | 1998-11-11 | Cor Therapeutics, Inc. | Selective factor xa inhibitors |
| JP2001521524A (ja) * | 1997-04-14 | 2001-11-06 | シーオーアール セラピューティクス インコーポレイテッド | 選択的Ｘａ因子阻害剤 |
| WO1998046591A1 (fr) * | 1997-04-14 | 1998-10-22 | Cor Therapeutics, Inc. | INHIBITEURS SELECTIFS DU FACTEUR Xa |
| US6294549B1 (en) | 1997-07-23 | 2001-09-25 | Merck & Co., Inc. | Method for eliciting an αvβ5 or dual αvβ3/αvβ5 antagonizing effect |
| AU742853B2 (en) * | 1997-07-31 | 2002-01-17 | Ube Industries, Ltd. | N-acylamino acid amide compounds and intermediates for preparation thereof |
| US6228854B1 (en) | 1997-08-11 | 2001-05-08 | Cor Therapeutics, Inc. | Selective factor Xa inhibitors |
| US6218382B1 (en) | 1997-08-11 | 2001-04-17 | Cor Therapeutics, Inc | Selective factor Xa inhibitors |
| US6333321B1 (en) | 1997-08-11 | 2001-12-25 | Cor Therapeutics, Inc. | Selective factor Xa inhibitors |
| US6129932A (en) * | 1997-09-05 | 2000-10-10 | Merck & Co., Inc. | Compositions for inhibiting platelet aggregation |
| GB2328871A (en) * | 1997-09-05 | 1999-03-10 | Merck & Co Inc | Compositions for inhibiting platelet aggregation |
| GB2328873A (en) * | 1997-09-08 | 1999-03-10 | Merck & Co Inc | The use of [3(R)-[2-(piperidin-4-yl)ethyl]-2-piperidone-1]acetyl-3(R)-methyl-ß-alanine for inhibiting blood platelet aggregation |
| CA2309204A1 (fr) * | 1997-11-26 | 1999-06-03 | Dupont Pharmaceuticals Company | 1,3,4-thiadiazoles et 1,3,4-oxadiazoles utilises comme antagonistes de .alpha.v.beta.3 |
| US6066648A (en) | 1997-12-17 | 2000-05-23 | Merck & Co., Inc. | Integrin receptor antagonists |
| US6211191B1 (en) | 1997-12-17 | 2001-04-03 | Merck & Co., Inc. | Integrin receptor antagonists |
| US6017926A (en) * | 1997-12-17 | 2000-01-25 | Merck & Co., Inc. | Integrin receptor antagonists |
| US6048861A (en) | 1997-12-17 | 2000-04-11 | Merck & Co., Inc. | Integrin receptor antagonists |
| US6623981B2 (en) * | 1998-01-27 | 2003-09-23 | Bristol-Myers Squibb Company | Detection of patients at risk for developing integrin antagonist/agonist mediated disease states |
| US6984635B1 (en) | 1998-02-13 | 2006-01-10 | Board Of Trustees Of The Leland Stanford Jr. University | Dimerizing agents, their production and use |
| WO2000000481A1 (fr) | 1998-06-29 | 2000-01-06 | Du Pont Pharmaceuticals Company | Isoxazolidines et carbamates cycliques utilises comme antagonistes de iib/iiia |
| AU748621B2 (en) * | 1998-08-13 | 2002-06-06 | Merck & Co., Inc. | Integrin receptor antagonists |
| US6303609B1 (en) | 1998-11-18 | 2001-10-16 | Dupont Pharmaceuticals Company | Isoxazoline fibrinogen receptor antagonists |
| US6319937B1 (en) | 1998-11-18 | 2001-11-20 | Dupont Pharmaceuticals Company | Isoxazoline fibrinogen receptor antagonists |
| US6723711B2 (en) | 1999-05-07 | 2004-04-20 | Texas Biotechnology Corporation | Propanoic acid derivatives that inhibit the binding of integrins to their receptors |
| CZ304225B6 (cs) * | 1999-05-07 | 2014-01-15 | Encysive Pharmaceuticals Inc. | Deriváty kyseliny propionové, které inhibují vazbu integrinů na jejich receptory |
| US6972296B2 (en) | 1999-05-07 | 2005-12-06 | Encysive Pharmaceuticals Inc. | Carboxylic acid derivatives that inhibit the binding of integrins to their receptors |
| EP1187592B1 (fr) | 1999-06-02 | 2007-08-01 | Merck & Co., Inc. | Antagonistes du recepteur de l'alpha v integrine |
| EP1212331B1 (fr) | 1999-08-24 | 2004-04-21 | Ariad Gene Therapeutics, Inc. | Analogues d'epirapamycine-28 |
| US7067526B1 (en) | 1999-08-24 | 2006-06-27 | Ariad Gene Therapeutics, Inc. | 28-epirapalogs |
| JP2003510360A (ja) | 1999-10-04 | 2003-03-18 | メルク エンド カムパニー インコーポレーテッド | インテグリン受容体拮抗薬 |
| US6518244B2 (en) | 2000-03-09 | 2003-02-11 | Intimax Corporation | Combinations of heparin cofactor II agonist and platelet IIb/IIIa antagonist, and uses thereof |
| AR030817A1 (es) | 2000-10-02 | 2003-09-03 | Novartis Ag | Derivados de diazacicloalcanodiona |
| US7232924B2 (en) * | 2001-06-11 | 2007-06-19 | Xenoport, Inc. | Methods for synthesis of acyloxyalkyl derivatives of GABA analogs |
| US7186855B2 (en) * | 2001-06-11 | 2007-03-06 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| US6818787B2 (en) * | 2001-06-11 | 2004-11-16 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| US8048917B2 (en) | 2005-04-06 | 2011-11-01 | Xenoport, Inc. | Prodrugs of GABA analogs, compositions and uses thereof |
| DE60229393D1 (de) * | 2001-07-18 | 2008-11-27 | Merck & Co Inc | Überbrückte piperidinderivate als melanocortin-rezeptor-agonisten |
| SI21096B (sl) * | 2001-10-09 | 2012-05-31 | Encysive Pharmaceuticals Inc | Derivati karboksilne kisline ki inhibirajo vezavo integrinov na njihove receptorje |
| UA78974C2 (en) | 2001-10-20 | 2007-05-10 | Boehringer Ingelheim Pharma | Use of flibanserin for treating disorders of sexual desire |
| US10675280B2 (en) | 2001-10-20 | 2020-06-09 | Sprout Pharmaceuticals, Inc. | Treating sexual desire disorders with flibanserin |
| EP1626961B1 (fr) * | 2003-05-17 | 2011-11-02 | Korea Research Institute of Bioscience and Biotechnology | Nouveaux composes 2-oxo-heterocycliques et compositions pharmaceutiques contenant ces composes |
| PL1912650T3 (pl) | 2005-08-03 | 2018-01-31 | Sprout Pharmaceuticals Inc | Zastosowanie flibanseryny w leczeniu otyłości |
| US20070087061A1 (en) * | 2005-10-14 | 2007-04-19 | Medafor, Incorporated | Method and composition for creating and/or activating a platelet-rich gel by contact with a porous particulate material, for use in wound care, tissue adhesion, or as a matrix for delivery of therapeutic components |
| US20070086958A1 (en) * | 2005-10-14 | 2007-04-19 | Medafor, Incorporated | Formation of medically useful gels comprising microporous particles and methods of use |
| US20090312242A1 (en) | 2006-06-30 | 2009-12-17 | Ramiro Castro | Flibanserin for the treatment of urinary incontinence and related diseases |
| PE20091188A1 (es) | 2007-09-12 | 2009-08-31 | Boehringer Ingelheim Int | Compuesto 1-[2-(4-(3-trifluorometil-fenil)piperazin-1-il)etil]-2,3-dihidro-1h-benzimidazol-2-ona (flibanserina), sus sales de adicion y composiciones farmaceuticas que los contienen |
| CA2686480A1 (fr) | 2008-12-15 | 2010-06-15 | Boehringer Ingelheim International Gmbh | Nouveaux sels |
| EA021838B1 (ru) * | 2009-07-30 | 2015-09-30 | Лабораториос Салват, С.А. | Производные 2,5-пиперазиндиона в качестве ингибиторов apaf-1 |
| US9958458B2 (en) | 2010-12-27 | 2018-05-01 | Brown University | Therapeutic and diagnostic methods involving biglycan and utrophin |
| US11043823B2 (en) * | 2017-04-06 | 2021-06-22 | Tesla, Inc. | System and method for facilitating conditioning and testing of rechargeable battery cells |
| US10605101B2 (en) | 2017-09-12 | 2020-03-31 | United Technologies Corporation | Process of making integrally bladed rotor |
| US10792771B2 (en) | 2017-09-12 | 2020-10-06 | Raytheon Technologies Corporation | Method of making integrally bladed rotor |
| US10561736B1 (en) | 2019-01-09 | 2020-02-18 | Spiral Therapeutics, Inc. | Apoptosis inhibitor formulations for prevention of hearing loss |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2549999A1 (de) * | 1975-11-07 | 1977-05-12 | Boehringer Mannheim Gmbh | Piperidin-derivate und verfahren zu ihrer herstellung |
| FR2334358A1 (fr) * | 1975-12-12 | 1977-07-08 | Sogeras | Nouveaux medicaments derives de l'indole |
| US4064125A (en) * | 1976-10-29 | 1977-12-20 | E. R. Squibb And Sons, Inc. | Substituted amides having antiinflammatory activity |
| DE3065026D1 (en) * | 1979-05-23 | 1983-11-03 | Beecham Wuelfing Gmbh & Co Kg | Phenylsulphonamide derivatives, a process for their preparation and their use as medicines |
| KR880007441A (ko) * | 1986-12-11 | 1988-08-27 | 알렌 제이.스피겔 | 스피로-치환된 글루타르아미드 이뇨제 |
| US4879313A (en) * | 1988-07-20 | 1989-11-07 | Mosanto Company | Novel platelet-aggregation inhibitors |
| US5039805A (en) * | 1988-12-08 | 1991-08-13 | Hoffmann-La Roche Inc. | Novel benzoic and phenylacetic acid derivatives |
| US5084466A (en) * | 1989-01-31 | 1992-01-28 | Hoffmann-La Roche Inc. | Novel carboxamide pyridine compounds which have useful pharmaceutical utility |
| CA2008116C (fr) * | 1989-02-23 | 2001-11-20 | Thomas Weller | Derives de glycine |
| NZ234264A (en) * | 1989-06-29 | 1993-05-26 | Warner Lambert Co | N-substituted cycloalkyl and polycycloalkyl alpha-substituted trp-phe- and phenethylamine derivatives, and pharmaceutical compositions |
| US5064814A (en) * | 1990-04-05 | 1991-11-12 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Anti-thrombotic peptide and pseudopeptide derivatives |
| IL99537A (en) * | 1990-09-27 | 1995-11-27 | Merck & Co Inc | Fibrinogen receptor antagonists and pharmaceutical preparations containing them |
| IL99538A0 (en) * | 1990-09-27 | 1992-08-18 | Merck & Co Inc | Fibrinogen receptor antagonists and pharmaceutical compositions containing them |
-
1992
- 1992-04-27 HU HU9303145A patent/HUT68769A/hu unknown
- 1992-04-27 WO PCT/US1992/003463 patent/WO1992019595A1/fr not_active Application Discontinuation
- 1992-05-05 NZ NZ242609A patent/NZ242609A/en unknown
- 1992-05-05 IL IL101779A patent/IL101779A0/xx unknown
- 1992-05-06 YU YU47992A patent/YU47992A/sh unknown
- 1992-05-06 CN CN92104545A patent/CN1067883A/zh active Pending
- 1992-05-06 MX MXPA92002103A patent/MXPA92002103A/es unknown
- 1992-05-06 CA CA002068064A patent/CA2068064C/fr not_active Expired - Fee Related
- 1992-05-07 AU AU16111/92A patent/AU647618B2/en not_active Ceased
- 1992-05-07 EP EP92304113A patent/EP0512831B1/fr not_active Expired - Lifetime
- 1992-05-07 ES ES92304113T patent/ES2137175T3/es not_active Expired - Lifetime
- 1992-05-07 AT AT92304113T patent/ATE184874T1/de active
- 1992-05-07 JP JP4158496A patent/JP2531562B2/ja not_active Expired - Lifetime
- 1992-05-07 DE DE69230013T patent/DE69230013T2/de not_active Expired - Fee Related
- 1992-05-07 KR KR1019920007683A patent/KR920021531A/ko not_active Application Discontinuation
- 1992-07-01 IE IE146392A patent/IE921463A1/en not_active Application Discontinuation
- 1992-11-06 US US07/972,668 patent/US5281585A/en not_active Expired - Fee Related
-
1993
- 1993-11-02 BG BG98194A patent/BG98194A/bg unknown
- 1993-11-05 FI FI934894A patent/FI934894A0/fi unknown
- 1993-11-05 NO NO1993933999A patent/NO933999D0/no unknown
- 1993-12-20 US US08/169,947 patent/US5455243A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| NO933999L (no) | 1993-11-05 |
| CA2068064C (fr) | 2001-01-02 |
| WO1992019595A1 (fr) | 1992-11-12 |
| MXPA92002103A (es) | 2005-08-25 |
| EP0512831B1 (fr) | 1999-09-22 |
| IL101779A0 (en) | 1992-12-30 |
| ATE184874T1 (de) | 1999-10-15 |
| DE69230013D1 (de) | 1999-10-28 |
| ES2137175T3 (es) | 1999-12-16 |
| BG98194A (bg) | 1994-09-30 |
| NO933999D0 (no) | 1993-11-05 |
| AU1611192A (en) | 1992-11-12 |
| CN1067883A (zh) | 1993-01-13 |
| JP2531562B2 (ja) | 1996-09-04 |
| EP0512831A1 (fr) | 1992-11-11 |
| AU647618B2 (en) | 1994-03-24 |
| FI934894A (fi) | 1993-11-05 |
| US5281585A (en) | 1994-01-25 |
| KR920021531A (ko) | 1992-12-18 |
| HU9303145D0 (en) | 1994-01-28 |
| HUT68769A (en) | 1995-07-28 |
| NZ242609A (en) | 1995-04-27 |
| US5455243A (en) | 1995-10-03 |
| JPH069525A (ja) | 1994-01-18 |
| DE69230013T2 (de) | 2000-04-27 |
| CA2068064A1 (fr) | 1992-11-08 |
| FI934894A0 (fi) | 1993-11-05 |
| YU47992A (sh) | 1995-03-27 |
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